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Wang M.,University of Saskatchewan | Doucette J.R.,University of Saskatchewan | Doucette J.R.,Cameco Multiple Sclerosis Neuroscience Research Center | Nazarali A.J.,University of Saskatchewan | Nazarali A.J.,Cameco Multiple Sclerosis Neuroscience Research Center
Cellular and Molecular Neurobiology | Year: 2011

Hoxa2 gene was reported to be expressed by oligodendrocytes (OLs) and down-regulated at the terminal differentiation stage during oligodendrogenesis in mice (Nicolay et al. 2004b). To further investigate the role of Hoxa2 in oligodendroglial development, a tetracycline regulated controllable expression system was utilized to establish a stable cell line (CG4-SHoxa2 [sense Hoxa2]), where the expression level of Hoxa2 gene could be up-regulated. The impact of Hoxa2 over-expression on the proliferation and differentiation of CG4-SHoxa2 cells was investigated. Up-regulation of Hoxa2 increased the proliferation of CG4-SHoxa2 cells. The mRNA levels of PDGFαR (platelet-derived growth factor [PDGF] alpha receptor), which is expressed by OL progenitor cells, were not different in CG4-SHoxa2 cells compared to wild-type CG4 cells. Semi-quantitative RT-PCR revealed that the mRNA levels of myelin basic protein (MBP) was lower in CG4-SHoxa2 cells than in wild-type CG4 cells indicating the differentiation of CG4-SHoxa2 cells was delayed when the Hoxa2 gene was up-regulated. © 2011 Springer Science+Business Media, LLC. Source


Carlson R.J.,University of Saskatchewan | Doucette J.R.,University of Saskatchewan | Doucette J.R.,Cameco Multiple Sclerosis Neuroscience Research Center | Nazarali A.J.,University of Saskatchewan | Nazarali A.J.,Cameco Multiple Sclerosis Neuroscience Research Center
Cellular and Molecular Neurobiology | Year: 2014

Pharmacogenomics has a significant potential to impact how we treat diseases. It involves targeting genetically identifiable populations with therapeutic interventions that promises to yield immediate positive health outcomes with lower or no side effects. The ‘trial and error’ method of treatment will no longer be necessary with the successful implementation of personalized medicine. The following is an overview of some new developments in pharmacogenomics of multiple sclerosis, and how it has the potential to improve future treatment. © 2014, Springer Science+Business Media New York. Source


Carlson R.J.,University of Saskatchewan | Doucette J.R.,University of Saskatchewan | Doucette J.R.,Cameco Multiple Sclerosis Neuroscience Research Center | Knox K.,University of Saskatchewan | And 3 more authors.
Cytokine and Growth Factor Reviews | Year: 2015

Multiple sclerosis (MS) is a progressive disorder of the central nervous system, often resulting in significant disability in early adulthood. The field of pharmacogenomics holds promise in distinguishing responders from non-responders to drug treatment. Most studies on genetic polymorphisms in MS have addressed treatment with interferon-β, yet few findings have been replicated. This review outlines the barriers that currently hinder the validity, reproducibility, and inter-study comparison of pharmacogenomics research as it relates to the use of interferon-β. Notably, statistical power, varying definitions of responder status, varying assay and genotyping methodologies, and anti-interferon-β neutralizing antibodies significantly confound existing data. Future work should focus on addressing these factors in order to optimize interferon-β treatment outcomes in MS. © 2014 Elsevier Ltd. Source

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